Stem Cell transplants and auto-immune disease

Stem cell transplants are at the leading edge of medical science for a host of diseases, including auto-immune diseases. Stem cells are cells that grow into a variety of other cells as needed.

A brief glossary of useful words may help understand the following articles.

Autologous Stem Cells. These are Stem cells that are taken from the patient, purified, multiplied, and then reinduced into the patient.

Allogeneic stem cells are those from a person other than the patient.

Hematopoietic Stem Cells are cells derived from the blood, usually from the bone marrow.

Mesenchymal Stem cells are multi-potent stromal cells that can differentiate into a variety of cell types. Often these have ben obtained from umbilical cord tissue.

Immunoablation is the shutting down or destroying of the patient's own immune system, usually by radiation. Following the immunoablation, the stem cells are transplanted, and the immune system is re-started. This is a very intensive and dangerous operation, with risk of mortality.

 

Hematapoetic stem cells

Interesting article indicates that Hematapoetic stem cell transplant works against rheumatic autoimmune diseases, but is very intensive, as generally the patients own immune system is deliberately shut down first. Suggests a 7% mortality from immunoablation conditioning treatment. (Hugle, Van Laar 2008) [1]

Mesenchymal stem cells

Although the studies are very few, the results have been very promising.  A 2011 a paper published by Annals of Rheumatic Diseases details a small study of 10 persons applying particularly to PM and DM.  It concludes that allogenic "MSCT appears safe and effective in drug-resistant patients with DM/PM".  (Wang, Zhang, 2011) [2]

Adipose Mesenchymal stem cells
Also in 2011 a paper published in the Journal of Translational Medicine shows stem cell treatment by a culture expanded autologous MSC tissue is safe, and somewhat effective for auto-immune disease, including polymyositis (Ra 2011). [3] The exciting thing about Mesenchymal stem cell transplants is that it does NOT require immunoalblative therapy with the resulting side effects. The paper is heaviily footnoted and well writtten, but several of the authors have a vested commercial interest in the patents on the technology being revealed.

Mesenchymal stem cells are adaptive to their environment

A review which surveys a brief history of MSCs, their anti-inflammatory, immunomodulatory and paracrine effects, and the current status of MSC-based therapies for a multitude of clinical applications. The availability and versatility of these remarkable cells make them an excellent treatment option for a wide variety of clinical pathologies (Murphy, Moncivais 2013). [7]

Migration or 'homing' of mesenchymal stem cells
Full article on MSCs that delves into the way stem cells migrate to the place of tissue destruction to effect the repair. One thing I notice is the mention of the possible importance of the telomeres in establishing the local environment. I noticed it because of research I have been doing on Alpha linoic acid increasing telomere length and functionality. Also interesting, it suggests adipose MSCs may be easier to harvest, and may be more effective at immune-modulation than marrow MSCs, stating "In humans, systemic administration of autologous human AdMSCs is a promising alternative to treat patients with autoimmune diseases including autoimmune ear disease, MS, polymyositis, atopic dermatitis, and RA (Ra 2011). [3]

Another article on the homing capacity of aMSC from RNL Bio. It shows that homing capacity of aMSC may be influenced by pre-treatment in vitro with chemokines (Baek, Kang 2011) [4]

Efficacy of hMSC in other auto-immune diseases

hMSCT appears safe and beneficial in small study of lupus patients.  The authors conclude "Significant reduction in disease activity was achieved in all patients, and there has been no recurrence to date and no treatment-related deaths.Our findings indicate that UC MSCT results in amelioration of disease activity, serologic changes, and stabilization of proinflammatory cytokines." (Sun, Wang 2010) [5]

Animal studies

Adipose MSC appear safe and effective in reducing imflammation in Crohns in mice . "ASCs decreased a wide panel of inflammatory cytokines and chemokines and increased interleukin-10 levels (P < .001), directly acting on activated macrophages. hASCs also impaired Th1 cell expansion and induced/activated CD4+CD25+FoxP3+ regulatory T cells with suppressive capacity on Th1 effector responses in vitro and in vivo (P < .001)." [6]

Stem cell exudates may be nearly as potent as the cells themselves

It is interesting to note that some researchers are demonstrating that the exudates produced by the MSCs are actually extremely beneficial - in some cases almost as beneficial as the actual stem cells themselves. (Riordan etc XXXX) [8]

Immunomodulation benefit may survive longer than the cells themselves.

One shortcoming of MSC therapy has been that the MSCs themselves are relatively short lived, and will not survive more than a year or two at most. Research recently published by Gonzalez et al sheds new light on this, and suggests the immunomodulatory effects of MSC treatment may in fact outlast the life of the transplanted cells, thus minimising this defecit.(Gonzalez 2015) [9]

 

Footnotes:

1. Hugle, Thomas, van Laar H. Stem cell transplantation for rheumatic autoimmune diseases. Arthritis Research & Therapy, 10:217, 2008 as found at VIEW

2. Wang, Dandan, Zhang H,Cao M,Tang Y,Liang J,Feng X,Wang H,Hua B,Liu B, sun L. Efficacy of Allogeneic Mesenchymal Stem Cell Transplantation in Patients with Drug-resistant Polymyositis and Dermatomyositis. Ann Rheum Dis., 70(7):1285-1288, 2011 as found at VIEW

3. Ra, Jeong Chan, Kang SK,Shin IS,Park HG,Joo SA,Kim JG,Kang BC,Lee YS,Nakama K,Piao M,Sohl B,Kurtz A. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. Journal of Translational Medicine, 9:181, 2011 as found at VIEW

4. Sun Jin Baek, Kang SK, Ra JC. n vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors. Experimental & Molecular Medicine, 43, 596-603, 2011 as found at VIEW

5. Lingyun Sun, Jun Liang1,Huayong Zhang1,Xuebing Feng1,Hong Wang1,Bingzhu Hua1,Bujun Liu1,Shengqin Ye2,Xiang Hu2,Wenrong Xu3,Xiaofeng Zeng4,Yayi Hou5,Gary S. Gilkeson6,Richard M. Silver6,Wang D.,Liang J.,Zhang H.,Feng X.,Wang H.,Hua B.,Liu B.,Ye S.,Hu X.,Xu W.,Zeng X.,Hou Y.,Gilkeson G. S.,Silver R. M.,Lu L, Shi S. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis & Rheumatism, Volume 62, Issue 8, pages 2467–2475, 2010 as found at VIEW

6. Manuel A. González, Gonzalez-Rey E,Rico L,Buscher D,Delgado M. Adipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses. Gastroenterology, Volume 136, Issue 3, Pages 978–989, 2009 as found at VIEW

7. Murphy, Matthew, Moncivais K, Caplan a. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Experimental & Molecular Medicine, 45, e54, 2013 as found at VIEW

8. Madrigal M, Kosagisharaf S Rao,Riordan N. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture m. Journal of Translational Medicine , 12:260, 2015 as found at VIEW

9. Rafael Gonzalez, Woynarowski D,Geffner L. Stem Cells Targeting Inflammation as Potential Anti-aging Strategies and Therapies. Cell & Tissue Transplantation & Therapy, 2015:7 1–8, 2015 as found at VIEW